We will continue to explore our hypothesis concerning the possible role of neurotoxic metabolites derived from psychotomimetic amines in the mode of action of this class of compound by pursuing the following goals: (1) With the aid of the liquid chromatography-electrochemical assay presently being established, we will examine the effects of DOM and its key metabolites (the hydroquinone, quinone, iminoquinone and indole) on brain biogenic amines. We hope to reveal regioselective alterations of biogenic amine metabolism in the brains of animals treated with these compounds. (2) The reversible binding of DOM and its metabolites to brain macromolecules will be explored with high specific activity (ca 10 ci/mmole) compounds now available by the tritiation reaction described in the progress report. The results should help determine if the in vitro data establishing the macromolecular alkylating properties of the 6-hydroxydopamine-like metabolites derived from DOM are applicable to the in vivo activity of DOM. (3) The chemical and biological (neurotoxic) properties of the family of 6-hydroxydopamine analogs described in the progress report will be examined in order to better understand the molecular action of 6-hydroxydopamine.